Angiogenic gene transfer is currently being investigated in clinical trials to treat critical limb ischemia (CLI). Gene transfer of plasmid DNA encoding angiogenic factors such as VEGF to ischemic limbs has shown promising results in preclinical animal models. However, large amounts of DNA, injected in large volumes are required to achieve meaningful gene expression, presenting significant safety and efficacy issues with this approach. Within the last several years in vivo electroporation (EP) has emerged as a method to dramatically enhance and provide precise control over location of plasmid DNA transfer into muscle. The goal of this Phase 1 investigation is directed at the development of Ichor's TriGrid(TM) EP technology as a clinically superior method to deliver angiogenic plasmids to skeletal muscle. Using the rat model of limb ischemia, plasmid DNA encoding VEGF will be transfected into ischemic hind limb, comparing simple plasmid injection with EP enhanced delivery. Success criteria will be to demonstrate effective angiogenesis as measured by improved blood flow and capillary development with significantly less DNA and in smaller volumes. Phase II development will move to the rabbit model and continue to optimize a delivery regimen that can customize angiogenesis to precise levels and locations of ischemic tissue.